I. Field of the Invention
The invention relates to the fields of pathology, virology, molecular biology and pharmaceuticals. More specifically, the invention relates to the identification of candidate inhibitors for the treatment and prevention of herpesvirus diseases. Also provided are compounds having such activity.
II. Related Art
Herpesviridae is a large family of DNA viruses that cause diseases in vertebrates, including humans. These viruses are significant pathogens and, in addition to primary infections, cause latent, recurring infections. At least six species of Herpesviridae—herpes simplex virus 1 (HSV-1) and HSV-2 (both of which can cause orolabial herpes and genital herpes), Varicella-zoster virus (which causes chickenpox and shingles), Epstein-Barr virus (which causes mononucleosis), Cytomegalovirus (which causes mental retardation and deafness in neonates), and Human herpesvirus 6 (which causes roseola infantum and febrile seizures)—are extremely widespread among humans. More than 90% of adults have been infected with at least one of these, and a latent form of the virus remains in most people. Other viruses with human tropism include human herpesvirus 7 and Kaposi's sarcoma-associated herpesvirus. There are more than 130 herpesviruses, including those that infect non-human mammals, birds, fish, reptiles, amphibians, and molluscs.
The drugs, acyclovir and ganciclovir, are considered the standard treatments and prophylactic agents for infections caused by HSV, VZV and CMV. Until a decade ago, the impact of acyclovir on the control of severe and life-threatening herpesvirus infections was unprecedented. Recently, approval of new drugs (i.e., penciclovir and the oral prodrugs, valaciclovir, famciclovir, cidofovir, fomivirsen, and foscarnet) has increased the number of therapeutic options for medical practitioners. Newer agents, such as brivudin and benzimidavir, are in ongoing clinical development, while others have been suspended because of safety concerns. Regardless, new anti-herpes agents are needed to face clinical issues such as drug resistance, increased use of anti-herpes prophylaxis, and safety concerns in small children or pregnant women.